This is a multicenter, randomized, double blind; active-controlled parallel groups study
enrolling subjects with primary hypercholesterolemia. Subjects receive ezetimibe,
simvastatin, or the combination once daily for 8 weeks to determine the effect on
LDL-cholesterol.
Inclusion Criteria:
- Subjects must demonstrate their willingness to participate in the study and comply
with its procedures by signing a written informed consent.
- Subjects must be >= 18 years and <= 75 years of age.
- Subjects with Primary Hypercholesterolemia must be finished the Lab test listed below
and the results must be available at the time of randomization at Visit 3 (Baseline
Visit).
- LDL-C concentration > 3. 64 mmol/L (140mg/dL) to <= 6. 3 mmol/L (250 mg/dL) using
the Friedewald calculation
- Total cholesterol (TC) > 5. 2mmol/L (200mg/dL) to < 12. 7mmol/L (500mg/dL)
- Triglyceride concentrations of <= 3. 99 mmol/L (350 mg/dL)
- Liver transaminases (ALT, AST) must be within normal limits, with no active liver
disease and CK < 50% above the upper limit of normal
- Clinical laboratory tests (CBC, blood chemistries, urinalysis) must be within
normal limits
- Subjects must report a stable weight history for at least 4 weeks prior to entry into
study at Visit 3 (Baseline Visit).
- Women of childbearing potential (includes women who are less than 1 year
postmenopausal and women who become sexually active) must be using an acceptable
method of birth control (e. g. medically prescribed IUD, condom in combination with
spermicide) or be surgically sterilized (e. g., hysterectomy or tubal ligation).
- Subjects must be free of any clinically significant diseases other than hyperlipidemia
that would interfere with study evaluations.
- Subjects must understand and be able to adhere to the dosing and visit schedules, and
must agree to remain on a cholesterol-lowering diet for the duration of the study.
Exclusion Criteria:
- Subjects whose body mass index (BMI = weight [kg]/height2 [m]) is >= 30 Kg/m^2 at
Visit 3 (Baseline Visit).
- Subjects who have known hypersensitivity to HMG-CoA reductase inhibitors.
- Subjects who consume > 14 alcoholic drinks per week. (A drink is: a can of beer, glass
of wine, or single measure of spirits).
- Any condition or situation, which in the opinion of the investigator, might pose a
risk to the subject or interfere with participation in the study.
- Women who are pregnant or nursing
- Subjects who have not observed the designated washout periods for any of the
prohibited medications outlined in protocol
- Congestive heart failure defined by NYHA as Class III or IV.
- Uncontrolled cardiac arrhythmia.
- Myocardial infarction, coronary bypass surgery or angioplasty within 6 months of study
entry.
- Unstable or severe peripheral artery disease within 3 months of study entry.
- Unstable angina pectoris within 6 months of study entry.
- Uncontrolled hypertension (treated or untreated) with systolic blood pressure > 160 mm
Hg or diastolic > 100 mm Hg of study entry.
- Uncontrolled (as determined by HbA1c > 7 %) or newly diagnosed (within 1month of study
entry) diabetes mellitus.
- Uncontrolled endocrine or metabolic disease known to influence serum lipids or
lipoproteins, i. e., secondary causes of hyperlipidemia, such as secondary
hypercholesterolemia due to hypothyroidism (TSH above upper limit of normal).
Subjects with a history of hypothyroidism who are on a stable therapy of thyroid
hormone replacement for at least 6 weeks are eligible for enrollment if TSH levels are
within normal limits before enrollment.
- Known Impaired renal function (plasma creatinine > 2. 0 mg/dL), or nephrotic syndrome
of study entry.
- Disorders of the hematologic, digestive, or central nervous systems including
cerebrovascular disease and degenerative disease that would limit study evaluation or
participation.
- Known HIV positive.
- Cancer within the past 5 years (except for successfully treated basal and squamous
cell carcinomas).
- History of mental instability, drug/alcohol abuse within the past 5 years, or major
psychiatric illness not adequately controlled and stable on pharmacotherapy.
- Subjects with known coagulopathy (PT and PTT at Visit 1 >1. 25 times control)
- Women receiving hormonal therapy, including hormone replacement, any estrogen
antagonist/agonist, or oral contraceptives.
- Any other condition which in the opinion of the investigator would make the patient
unsuitable for enrollment, or could interfere with the patient participating in and
completing the study.
